Resistance status of chloroquine, basoquine and sulphadoxine-pyremethamine against Plasmodium falciparum in Punjab, Pakistan was tested by in vivo and in vitro study techniques and found 38.6% resistance to chloroquine and 34.8% to basoquine. Sulphadoxine-pyrimethamine found effective with only 5.7% resistance. Comparison Traditional microscopy showed 4.47 % false positive detection (p<0.000) as compared to rapid drug test. As chloroquine and basoquine has crossed resistance percentage >10%, mono therapy with these drugs should be replaced with combination of artemether in Punjab, Pakistan.